Bone marrow, spleen, and cervical lymph nodes from animals that relapsed on continuous dasatinib therapy were analyzed for the presence of KD mutations. The frequency of the T315I mutation decreased with the reduced intensity of dasatinib treatment, whereas P-loop mutations were more commonly detected in mice receiving less intensified dasatinib schedules. In 3 separate leukemias in which both T315I and P-loop mutations were detected in the same tissue, both mutations were absent on the same sequenced amplicon, suggesting that they arose in independent leukemic clones rather than sequentially during the course of therapy. The tissues and nature of different KD mutations detected in individual mice within the 4 treatment arms are summarized in detail in supplemental Figure 3.